Interactions of metronidazole and chloramphenicol with myoglobin: Crystal structure of a Mb-acetamide product
Interactions of metronidazole and chloramphenicol with myoglobin: Crystal structure of a Mb-acetamide product
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甲硝唑和氯霉素与肌红蛋白的相互作用：Mb-乙酰胺产品的晶体结构
DOI：
10.1142/s1088424623500700
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发表时间：
2023
影响因子：
1.5
通讯作者：
Richter-Addo, George B.
中科院分区：
文献类型：
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作者：
Powell, Samantha M.;Prather, Kiana Y.;Nguyen, Nancy;Thomas, Leonard M.;Richter-Addo, George B.
硝基有机物由于其对健康的危害而引起人们对安全环境的普遍关注。然而，一些硝基有机物如甲硝唑（Mtz）和氯霉素（CAM）也具有药用价值。Mtz和CAM可能通过其亚硝基衍生物进行还原性生物活化。我们表明，使用紫外-可见光谱，抹香鲸肌红蛋白（swMb）和它的远端口袋突变体保留H-键合能力与Mtz反应的存在下，连二亚硫酸盐产生的产品与光谱暗示的铁结合亚硝基（铁RNO;420 nm）的形式。我们已经结晶并解决了H64 Q swMb-乙酰胺化合物的X-射线晶体结构，分辨率为1.76 μ m;该化合物的形成是由于偶然的晶体捕获，由血红素中心，从Mtz的还原分解的乙酰胺。只有一种swMb蛋白，即具有相对灵活的Gln 64残基的H64 Q swMb，与CAM反应，这可能是由于CAM的体积大，通常会限制其进入血红素位点。
Nitroorganics present a general concern for a safe environment due to their health hazards. However, some nitroorganics such as metronidazole (Mtz) and chloramphenicol (CAM) also possess medicinal value. Mtz and CAM can undergo reductive bioactivation presumably via their nitroso derivatives. We show, using UV-vis spectroscopy, that sperm whale myoglobin (swMb) and its distal pocket mutants retaining H-bonding capacity react with Mtz in the presence of dithionite to generate products with spectra suggestive of the Fe-bound nitroso (Fe–RNO;420 nm) forms. We have crystallized and solved the X-ray crystal structure of an H64Q swMb-acetamide compound to 1.76 Å resolution; the formation of this compound results from the serendipitous crystallographic trapping, by the heme center, of acetamide from the reductive decomposition of Mtz. Only one of the swMb proteins, namely H64Q swMb with a relatively flexible Gln64 residue, reacted with CAM presumably due to the bulky nature of CAM that generally may restrict its access to the heme site.